Recombinant Human Spastin (SPAST), partial

1. The findings suggest a mechanism for neurodegeneration in hereditary spastic paraplegia whereby SPAST mutations indirectly lead to impaired peroxisome transport and oxidative stress. PMID: 27229699
2. study to explore the novel SPAST splice site donor variant, c.1004+3A>C in spastic paraplegia type 4; Exon 6 is skipped out by the variant, leading to premature termination of translation, p.Gly290Trpfs*5; measurement of SPAST transcripts in lymphocytes demonstrated reduction through nonsense-mediated mRNA decay PMID: 28870597
3. Two novel mutations in gene SPG4 in patients with autosomal dominant spastic paraplegia PMID: 29368828
4. The N184X mutation triggers the reinitiation of translation at a third start codon in SPAST, resulting in synthesis of a novel M187 spastin isoform that is able to sever microtubules. PMID: 28495799
5. Our data reveal a high rate of complex cases (25%), with psychiatric disorders among the most common comorbidity (10% of all SPASTpatients). Further, we identify a genotype-phenotype correlation between patients carrying loss-of-function mutations in SPAST and the presence of psychiatric disorders. PMID: 28572275
6. Variants in SPAST and KIF5A were the most common causes of autosomal dominant hereditary spastic paraplegia in Greece. PMID: 26374131
7. Two distinct Alu insertion-associated deletions in the SPAST gene cause hereditary spastic paraplegia type SPG4. PMID: 26932189
8. The data of this study confirmed the genetic heterogeneity of childhood-onset pure HSP, with SPG4/SPAST and SPG3A/ATL1 being the most frequent forms. PMID: 27260292
9. We report the first genetic study of uncomplicated HSP patients from the Czech Republic. We found broad mutation spectrum in 13 from the 17 coding exons and adjacent regions of the SPAST gene. We detected 21 novel presumably pathogenic mutations. The high frequency of SPAST mutations was found only in familial patients. PMID: 27334366
10. This study demonstrted that the most frequently affected gene was SPAST with pathogenic or likely pathogenic mutations in hereditary spastic paraplegia. PMID: 27084228
11. This study demonstrated that SPAST gene mutation associated with hereditary spastic paraplegias in group of Polish patients PMID: 26671083
12. We identified two novel mutations and two previously reported mutations in SPAST and ATL1, respectively. The family with the ATL1 c.1204T>G mutation exhibited male-lethality, female infancy-onset, and pseudo- X-linked dominant transmission PMID: 26600529
13. Using human-engineered and differentially modified microtubules study finds that glutamylation is the main regulator of the hereditary spastic paraplegia microtubule severing enzyme spastin. PMID: 26875866
14. Patients with deletions of exons in the SPAST gene showed pure hereditary spastic paraplegia. PMID: 26165777
15. Novel SPAST pathogenic variants were identified in Korean patients with hereditary spastic paraplegia. PMID: 26208798
16. The coexistence of mutations in SPAST and FSHD was confirmed in our proband and in two siblings PMID: 25511172
17. The spastin as a microtubule-severing protein was an important mechanistic breakthrough, it seems certain that insufficient microtubule severing alone is not an adequate explanation for HSP-SPG4. PMID: 26094131
18. SPAST mutations are common in Chinese patients with pure hereditary spastic paraplegia PMID: 24824479
19. Data showed 3 micro-mutations and 2 exon deletions in SPAST gene and 2 micro-mutations in ATL1 gene in this cohort of Chinese patients with spastic paraplegia. PMID: 25454648
20. NA14 may act as an adaptor protein regulating SPG4 localization to centrosomes, temporally and spatially regulating the microtubule-severing activity of SPG4 that is particularly critical during the cell cycle and neuronal development. PMID: 25390646
21. ESCRT-III, VPS4 and spastin cooperate to coordinate nuclear envelope sealing and spindle disassembly at nuclear envelope-microtubule intersection sites during mitotic exit to ensure nuclear integrity and genome safeguarding PMID: 26040712
22. SPG4 appears to be the major cause of hereditary spastic paraplegia in Tuscany. PMID: 24731568
23. This study reported a novel splice-site mutation, c.1098+1~2GT-->CTCAGA, in the AAA domain of SPG4 in a Chinese family with pure autosomal dominant hereditary spastic paraplegia. PMID: 24659419
24. four novel mutations were identifiedin SPAST/SPG4. PMID: 24033003
25. analys of deletion mutation of SPAST in hereditary spastic paraplegias, correlation with increased tendon reflexes in the lower limbs and Babinski sign PMID: 24824741
26. Neurite complexity and maintenance in hereditary spastic paraplegia patient-derived neurons are critically sensitive to spastin gene dosage. PMID: 24381312
27. the Alu genomic architecture of SPAST predisposes to diverse intragenic copy-number variants alleles with distinct transcriptional--and possibly phenotypic--consequences. PMID: 25065914
28. successful establishment of human pluripotent stem cell-based neuronal models of SPG4, which will be valuable for dissecting the pathogenic cellular mechanisms and screening compounds to rescue the axonal degeneration in hereditary spastic paraplegias PMID: 24123785
29. This study identified the genetic cause in approximately 25 % of patients in this sample; this is a high proportion of cases, given that one of the most common causes of HSP (SPG4) had already been excluded. PMID: 23812641
30. Our study enlarges the number of pathogenic SPAST mutations, and confirms the association with a pure spastic paraplegia phenotype PMID: 22960362
31. This study demonistrated that toxicity of mutant spastin proteins, especially mutant M1, contributes to axonal degeneration in the corticospinal tracts. PMID: 24478365
32. a novel 14-bp heterozygous deletion that induced a frameshift mutation in exon 15 of SPAST is predicted to have functional impact and found to cosegregate with the disease phenotype of hereditary spastic paraplegia PMID: 23716148
33. The results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. PMID: 23897888
34. Data suggest that ATP-bound SPG4 interacts strongly/cooperatively with microtubules; this interaction stimulates ATP hydrolysis by SPG4; SPG4 then dissociates from microtubules and exchanges ADP for ATP in solution for next round/cycle. PMID: 23745751
35. Patients with SPG4-related hereditary spastic paraplegia are not found to have ophthalmological manifestations. PMID: 23238845
36. Compared to control cells, patient-derived cells had 50% spastin, 50% acetylated alpha-tubulin and 150% stathmin, a microtubule-destabilizing enzyme. PMID: 23264559
37. micro-rearrangements in the SPAST gene are a fairly frequent cause of hereditary spastic paraplaegia PMID: 22203332
38. study concludes that SPAST mutations are responsible for the majority of hereditary spastic paraplegia (HSP) in Australia; most of the patients with SPAST mutations had pure forms of HSP and a positive family history to suggest autosomal dominant HSP PMID: 23252998
39. analysis of spastin's microtubule-binding properties and comparison with katanin PMID: 23272056
40. The results of this study a a SPG4 mutation was higher than for patients with SPG3 mutations in patients with Autosomal dominant spastic paraplegias. PMID: 23400676
41. Data report here the 3.3 A X-ray crystal structure the AAA domain of human spastin (SPG4) and show that, despite amino acid differences in a number of key residues, the human and D. melanogaster spastin structures are highly conserved. PMID: 22446388
42. findings indicate that protrudin interacts with spastin and induces axon formation through its N-terminal domain; protrudin and spastin may work together to play an indispensable role in motor axon outgrowth PMID: 22573551
43. wild type spastin is even more sensitive toward the presence of inactive mutants than in enzymatic assays, suggesting a weak coupling of ATPase and severing activity. PMID: 22637577
44. transcriptional and post-transcriptional regulation of SPAST PMID: 22574173
45. Peripheral neuropathy occurs in hereditary spastic paraplegia patients with SPG4 mutations. PMID: 22192498
46. We identified seven different spastin mutations in five probands and one sporadic patient with Hereditary spastic paraplegia PMID: 21834905
47. Spastin was identified as a novel component of the HOXA10 transcriptional complex in Ishikawa nuclear extracts. PMID: 21757506
48. The results of this study showed that consistent with data suggesting that SPAST mutations mostly cause a pure HSP phenotype. PMID: 21546041
49. previously unreported autosomal dominant mutations in the spastin gene in hereditary spastic paraplegia PMID: 20718791
50. A higher level (78.8 +/- 3.9%) of functional spastin than the expected ratio of 50% owing to leaky splicing might cause late age at onset of hereditary spastic paraplegia. PMID: 20491894

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HGNC: 11233

OMIM: 182601

KEGG: hsa:6683

STRING: 9606.ENSP00000320885

UniGene: Hs.468091